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Vusolimogene Oderparepvec with Nivolumab for Advanced Melanoma Patients Whose Cancer Progressed After Previous Immunotherapy Treatments

Verified siteRegistered drugNo placebo
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What is this trial about?

A plain-language summary of the goals, design and what participants do

This study is evaluating a new treatment approach for advanced melanoma, a serious form of skin cancer that has spread or cannot be surgically removed. The treatment being studied combines vusolimogene oderparepvec (VO) with nivolumab in patients whose cancer has progressed despite previous treatments with anti-PD-1 and anti-CTLA-4 therapies. This combination will be compared to the physician's choice of treatment to determine if it can improve survival for patients with advanced melanoma.

The purpose of the study is to compare survival outcomes between patients receiving the VO and nivolumab combination versus standard treatments chosen by doctors. During the study, patients will be randomly assigned to receive either the combination therapy or the physician's choice of treatment. Patients will undergo regular assessments to monitor how their cancer responds to treatment and to check for any side effects.

The research process

The trial runs in 7 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Randomization

    After joining the study, you will be randomly assigned to one of two treatment groups: either vusolimogene oderparepvec (VO) in combination with nivolumab or the physician's choice of treatment for advanced melanoma (skin cancer that has spread or cannot be surgically removed).

    The randomization process is like flipping a coin to determine which treatment you will receive. You cannot choose your treatment group.

  2. Step 2

    Treatment Group A: VO + Nivolumab

    If assigned to this group, you will receive two medications:

    Vusolimogene oderparepvec (VO): This medication will be injected directly into your tumor(s). The doctor will identify suitable tumors that can be injected.

    Nivolumab (Opdivo): This is given as an intravenous (IV) infusion, which means it's administered through a vein. The typical dose is 10 mg/mL as a solution for infusion.

  3. Step 3

    Treatment Group B: Physician's Choice

    If assigned to this group, your doctor will select one of the following treatments based on what they believe is most appropriate for your condition:

    Pembrolizumab (Keytruda): Given as an IV infusion at 25 mg/mL

    Nivolumab + Relatlimab (Opdualag): Given as an IV infusion at 240 mg/80 mg

    Dacarbazine: Given as an injection or infusion at 100 mg

    Temozolomide: Given as capsules at 5 mg

    Paclitaxel: Given as an IV infusion at 6 mg/ml

  4. Step 4

    Treatment Schedule and Duration

    The treatment schedule will depend on which medication(s) you receive. Your healthcare team will explain the specific timing of your treatments.

    You will continue treatment until one of the following occurs: your disease progresses (gets worse), you experience unacceptable side effects, or you complete the planned treatment duration.

    The study is expected to continue until July 2025, with follow-up potentially extending to December 2030.

  5. Step 5

    Regular Assessments

    Throughout the study, you will have regular assessments to monitor your health and how the treatment is working. These include:

    Physical examinations: To check your overall health

    Blood tests: To monitor your blood counts, liver function, kidney function, and other health indicators

    Imaging scans: To measure tumor size and track changes over time using RECIST criteria (a standard way to measure if tumors are growing, shrinking, or staying the same)

  6. Step 6

    Monitoring for Side Effects

    Your healthcare team will closely monitor you for any side effects or adverse reactions to the treatment.

    You should report any new symptoms or changes in how you feel to your healthcare team, even if they seem minor.

    If you experience severe side effects, your treatment may be temporarily paused or permanently stopped.

  7. Step 7

    Follow-up Period

    After completing treatment, you will enter a follow-up period where your health will continue to be monitored.

    The follow-up assessments will track your long-term health and the lasting effects of the treatment.

    The study team will monitor your survival status for up to 3 years after treatment.

Who can join the trial?

16 criteria

  • You must be 12 years of age or older and weigh at least 25 kg (55 pounds).
  • You must have good physical functioning ability - an ECOG performance status of 0-1 for adults (meaning you can carry out light activities with minimal or no symptoms) or a Lansky score of 80 or higher for ages 12-17 (meaning you can participate in normal activities with some limitations).
  • You must have a life expectancy of at least 3 months.
  • You must meet specific contraception requirements:
    • Women who can become pregnant must use effective birth control during treatment and for up to 5-6 months after treatment, depending on the medications received
    • Men must follow specific contraception guidelines during treatment and for up to 6 months after, depending on the medications received
    • Adolescents (12-17 years) must follow age-appropriate contraception requirements
    • Women who can become pregnant must have a negative pregnancy test within 7 days before starting treatment.
    • You must be able to give informed consent and follow study requirements.
    • You must have advanced melanoma (skin cancer) that is unresectable (cannot be removed by surgery) or has spread (metastatic), classified as Stage IIIb through IV.
    • Your melanoma must have worsened while on previous immunotherapy treatments (anti-PD-1 and anti-CTLA-4 antibodies).
    • You must have known BRAF mutation status (a specific genetic change in the tumor) or agree to testing for it.
    • You must have at least one measurable tumor of at least 1 cm in size that can be injected with the study treatment.
    • You must have adequate blood cell counts, including acceptable white blood cell, neutrophil, platelet, and hemoglobin levels.
    • You must have adequate liver function as shown by blood tests.
    • You must have adequate kidney function as shown by blood tests.
    • Your blood clotting tests must be within acceptable ranges.

Who cannot join the trial?

10 criteria

  • You have had previous treatment with BRAF or MEK inhibitors (types of targeted cancer drugs)
  • You have had previous treatment with any anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 or any other drugs that affect your immune system's ability to fight cancer
  • You have had a major surgery within 4 weeks before starting the study treatment
  • You have active brain metastases (cancer that has spread to the brain) or spinal cord compression
  • You have an active autoimmune disease (a condition where your immune system attacks your own body)
  • You have a serious or uncontrolled medical condition that could interfere with the study
  • You require treatment with corticosteroids (more than 10 mg daily of prednisone or equivalent) or other immunosuppressive medications
  • You have interstitial lung disease (a group of disorders that cause scarring of lung tissues)
  • You have a history of organ transplant that requires ongoing immunosuppression
  • You are pregnant or breastfeeding
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Investigated drugs

  • Vusolimogene Oderparepvec (VO)

    is a type of therapy that uses a modified virus to specifically target and kill cancer cells. It works by injecting the therapy directly into tumors, where it can replicate inside cancer cells and cause them to break apart. It also helps stimulate the body's immune system to recognize and attack cancer cells throughout the body.

  • Nivolumab

    is an immunotherapy medication that works by blocking a protein called PD-1 on certain immune cells. By blocking this protein, nivolumab helps your immune system recognize and attack cancer cells. It's given as an intravenous (IV) infusion.

  • Physician's Choice Treatment

    refers to a treatment that your doctor will select based on what they believe is most appropriate for your specific situation. This could include various approved treatments for melanoma.

What is already known about the treatment

  • Vusolimogene Oderparepvec

    An investigational oncolytic viral therapy administered by direct injection into tumor sites, designed to selectively replicate in cancer cells and stimulate the immune system to attack the tumor. It is currently being studied in clinical trials for advanced melanoma, particularly in patients whose cancer has progressed despite prior immunotherapy treatments. Vusolimogene Oderparepvec works by infecting and breaking down cancer cells while also triggering an immune response against the tumor. This therapy belongs to the class of oncolytic virus immunotherapies, representing a novel approach to treating advanced melanoma by potentially enhancing the body's own immune response against cancer.

  • Nivolumab

    An intravenously administered immunotherapy medication that blocks the PD-1 protein on immune cells, helping the immune system recognize and attack cancer cells. Nivolumab is approved for treating several types of cancer including advanced melanoma and has shown significant efficacy in clinical practice. It works by preventing cancer cells from using the PD-1 pathway to hide from T cells, thereby restoring the immune system's ability to detect and fight cancer cells. Nivolumab belongs to the class of immune checkpoint inhibitors and is often used when melanoma has spread or cannot be removed by surgery.

Investigated diseases

Advanced Melanoma – A serious form of skin cancer that has spread beyond its original site to other parts of the body. It develops when melanocytes, the cells that produce the skin pigment melanin, grow uncontrollably. Advanced melanoma can metastasize to lymph nodes, organs, and other tissues. The disease typically progresses through stages where cancer cells invade deeper layers of skin and eventually spread through the lymphatic system or bloodstream. As it advances, it may cause symptoms including new or changing skin lesions, enlarged lymph nodes, and organ-specific symptoms based on where the cancer spreads. AI: Advanced Melanoma – A form of skin cancer that has spread beyond its original site to other parts of the body. It develops when melanocytes (pigment-producing cells) grow uncontrollably. Advanced melanoma begins in the skin but progresses by invading deeper tissue layers and spreading to lymph nodes, organs, and other tissues through the bloodstream or lymphatic system. As it advances, it may create new tumor sites in distant organs such as the lungs, liver, brain, or bones. Patients may experience symptoms related to both the primary tumor site and areas of metastasis.
Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2023-508612-29-00Protocol codeRP1-104Estimated enrolment315 patientsSponsorReplimune Group Inc.

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